The studies described in this proposal continue a program of integrated clinical and laboratory investigations of anticonvulsant drugs. The objective of this proposal is to extend our current understanding of the metabolism, efficacy and toxicity of these compounds. The major emphasis is upon clinical investigations with epileptic patients. The specific proposals relate to 2 areas of investigation. First, our observation that anticonvulsant drugs may enhance adrenal cortex secretion of cortisol will be further documented and extended with a series of studies designed to determine which drugs exert this effect, the mechanism by which adrenal cortical function is altered and the consequences of enhanced cortisol secretion. Secondly, the 2-desoxy derivative of phenytoin (Glior) will be studied in a cross-over clinical trial comparing its efficacy and toxicity to that of phenytoin. The metabolic pathway of Glior will be studied in animals and man with special emphasis upon induction. Finally, the effect of phenytoin and Glior upon cortisol secretion in man will be investigated. The information obtained from these studies will have direct practical clinical value for the treatment of epilepsy as well as extend our fundamental knowledge of the pharmacology of anticonvulsant drugs.